Strain Name: B6/JGpt-Lag3 emCin(hLAG3) /Gpt
Strain Type: Knock-in
Strain ID: T003597
1. Efficacy evaluation of human LAG3 inhibitors
2. Safety evaluation of human LAG3 inhibitors
3. Anti-tumor Drug Research and Development
4. Research on autoimmune diseases
LAG3（Lymphocyte activation gene 3）, a cell surface molecule expressed on activated T cells, NK cells, B cells and plasmacytoid dendritic cells. Studies have shown that knock out the LAG3 gene or in vivo antibodies blocking LAG3 function can increase the aggregation and effector function of antigen-specific CD8+ T cells in organs or tumors, Therefore, blocking LAG3 is a potential tumor treatment. B6-hLAG3 mice the ideal animal model to evaluate the efficacy of human LAG3 antibody.
Detection of LAG3 expression
hLAG3 homozygous mice expressed human LAG3 on both T and B cell surfaces.
T/B/NK cell ratio assay
The proportion of T/B/NK cells in B6-hLAG3 homozygous, heterozygous and wild type mice was basically the same.
Anti-tumor Efficacy Test
Evaluation of in vivo efficacy of Anti-hLAG3 by subcutaneous inoculation of MC38 model in B6-hLAG3 mice
Fig.4 In vivo efficacy test based on B6-hLAG3.
Murine colon cancer MC38 cells was cultured to logarithmic growth phase and inoculated subcutaneously into 6-8 weeks old B6-hLAG3 mice. Mice were divided into Vehicle groups, Anti-mPD1 groups, Anti-LAG3 groups and Anti-mPD1 + Anti-hLAG3 groups (n=6).When the tumor size reached about 100 mm3, mice were treated with the appropriate medication twice a week for a total of 6 times. Data are presented in Mean ± SEM format.
Result：Anti-mPD1 group, Anti-mPD1 group inhibit tumor growth, and Anti-mPD1 + Anti-hLAG3 group inhibited tumor growth (TGI = 19.13%, TGI = 21.13% and TGI = 40.69% respectively)(Fig.4, Left). The trend of weight change of different group is consistent (Fig.4,Right). The data indicated that B6-hLAG3 mice is the ideal animal model to evaluate the efficacy of human LAG3 antibody.
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